Cyclin-dependent protein kinase 5 (Cdk5) and the regulation of neurofilament metabolism

被引：103

作者：

Grant, P ^{[1
]}

Sharma, P ^{[1
]}

Pant, HC ^{[1
]}

机构：

[1] NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA

来源：

EUROPEAN JOURNAL OF BIOCHEMISTRY | 2001年 / 268卷 / 06期

关键词：

neurofilament; Cdk5; phosphorylation; cytoskeleton; neuron;

D O I：

10.1046/j.1432-1033.2001.02025.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cyclin-dependent kinase 5 (Cdk5), a complex of Cdk5 and its activator p35 (Cdk5/p35), phosphorylates diverse substrates which have multifunctional roles in the nervous system. During development, it participates in neuronal differentiation, migration, axon outgrowth and synaptogenesis. Cdk5, acting together with other kinases, phosphorylates numerous KSPXK consensus motifs in diverse cytoskeletal protein target molecules, including neurofilaments, and microtubule associated proteins, tau and MAPs. Phosphorylation regulates the dynamic interactions of cytoskeletal proteins with one another during all aspects of neurogenesis and axon radial growth. In this review we shall focus on Cdk5 and its regulation as it modulates neurofilament metabolism in axon outgrowth, cytoskeletal stabilization and radial growth. We suggest that Cdk5/p35 forms compartmentalized macromolecular complexes of cytoskeletal substrates, other neuronal kinases, phosphatases and activators ('phosphorylation machines') which facilitate the dynamic molecular interactions that underlie these processes.

引用

页码：1534 / 1546

页数：13

共 150 条

[1] Hyperphosphorylated tan and neurofilament and cytoskeletal disruptions in mice overexpressing human p25, an activator of cdk5 [J].